Knowledge of how the genetics of vector populations condition the spread of arboviruses is critical for understanding dynamics of disease incidence, development of risk assessment strategies for novel virus introductions and development of virus transmission biomarkers that can be used to efficiently target control efforts. Since its introduction in 1999, West Nile Virus (WNV) has spread completely across the contiguous United States and has been responsible for over 23,000 confirmed human cases with almost 900 deaths. The most efficient laboratory vector has been demonstrated to be Culex tarsalis, which has been identified as a very important vector in the western United States. Prior studies and our preliminary data have demonstrated significant genetic structure among Cx. tarsalis populations and geographic variation in the ability of Cx. tarsalis to transmit WNV orally and vertically. We hypothesize that genetic variation related to vector competence is partly responsible for temporal and spatial variation seen in WNV transmission in Cx. tarsalis. We will use the Cx. tarsalis/WNV relationship as a model system to investigate how the genetics of mosquito populations govern the successful invasion and maintenance of an introduced arbovirus in natural populations. We have developed multiple genetic marker systems for use in Cx. tarsalis. Our specific aims are to: 1) Conduct population genetic analysis of Cx. tarsalis populations using mitochondrial sequence data and our newly-developed microsatellite markers, 2) Identify quantitative trait loci (QTL) responsible for WNV vector competence in Cx. tarsalis using an Advanced Intercross Design and 3) Identify QTL explaining WNV vector competence in natural Cx. tarsalis populations. Our results will guide future efforts to identify and validate specific candidate genes responsible for WNV susceptibility in Cx. tarsalis, determine the role of specific genes in maintaining WNV transmission in natural Cx. tarsalis populations and understand how the genetics of natural vector populations condition the successful introduction and maintenance of introduced exotic pathogens. Our work will ultimately lead to the identification of mosquito genetic biomarkers for WNV transmission that can be used for risk assessment and effective targeting of vector control efforts. This work also has important relevance for bioterrorism issues because it will provide insight into how intrinsic vector genetic factors in mosquito populations affect the epidemiology of a released Category B agent.